This research program will examine the underlying biochemical defects and accompanying changes in ultrastructural morphology occurring in the central nervous system after experimental intoxication with organic mercurial compounds. The effects of methyl mercury (MeHg) on synaptosome fraction protein synthesis, respiration, DNA synthesis and amino acid uptake will be examined in detail. A possible proximate event in the methyl mercury lesion is the inhibition of DNA synthesis. The mitochondrion is the prime locus for such synthesis and characterization of this inhibition in adult and neonates following administration of MeHg in vivo will be undertaken. These biochemical investigations will be correlated with electron microscopic observations on cerebellar and cerebral synaptogenesis.